idh1 mutation
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Author(s):  
Michael Drumm ◽  
Jessica W Templer ◽  
Matthew Tate ◽  
Lawrence Jennings ◽  
Craig Horbinski
Keyword(s):  

2022 ◽  
pp. 110141
Author(s):  
Jie Wang ◽  
Yue Hu ◽  
Xuejun Zhou ◽  
Shanlei Bao ◽  
Yue Chen ◽  
...  
Keyword(s):  
Dce Mri ◽  

JCI Insight ◽  
2021 ◽  
Author(s):  
Christoph Trautwein ◽  
Laimdota Zizmare ◽  
Irina Mäurer ◽  
Benjamin Bender ◽  
Björn Bayer ◽  
...  

2021 ◽  
pp. 100812
Author(s):  
Sajad Najafi ◽  
Sajjad Esmaeili ◽  
Hossein Zhaleh ◽  
Yazdan Rahmati

2021 ◽  
Vol 3 (Supplement_6) ◽  
pp. vi10-vi10
Author(s):  
Shinichiro Koizumi ◽  
Ippei Makita ◽  
Tetsuro Sameshima ◽  
Kazuhiko Kurozumi

Abstract Introduction: The cancer gene panel test was covered by insurance in June 2019. Our institution started the test in May 2020 and has experienced 10 cases, so we will report on the current status and future prospects. Methods: The subjects were 10 patients who underwent the cancer gene panel test using FoundationOne CDx. Results:The cases included 8 glioblastomas, an anaplastic astrocytoma, and an anaplastic oligodendroglioma. The total number of tumor mutational burden (TMB) was judged to be low in all cases, and the microsatellite instability test (MSI) showed no instability in all cases (MSI-Stable). The total number of genetic changes detected was 11 ± 5.0, oncogene mutations were 5.3 ± 2.4, and gene mutations of unknown relevance to cancer were 5.7 ± 2.8. Major oncogene mutations were IDH1 mutation in 4 cases, ATRX mutation in 2 cases, TP53 mutation in 6 cases, and BRAF V600E mutation in 1 case. Based on the test results, a 25-year-old man with BRAF V600E mutation was initiated into the NCCH1901 study (Patient-Proposed Healthcare Services). A case with IDH1 mutation (47-year-old male) entered a phase I clinical trial of a mutant IDH1 inhibitor. It is estimated that the chance of finding an appropriate drug by cancer gene panel test is about 10–20%. However, in cases that are resistant to standard treatment, the benefits can be expected if the drugs associated with the cancer gene panel test can be used. Conclusions: Although Malignant gliomas are often TMB-low and MSI-stable and the response rate to molecular-targeted drugs and other therapies is not high, there are some cases that can be salvaged by performing the cancer gene panel test. It is suggested that the active use of cancer gene panel test may contribute to the development of new drugs with high response rates and the improvement of prognosis.


2021 ◽  
Vol 67 (3) ◽  
pp. 92-98
Author(s):  
Amal Ezzat Abd El-Lateef ◽  
Manar M. Ismail ◽  
Mohammed Almohammadi ◽  
Amr M. Gawaly

Despite the great advance in treatment, cytogenetically normal Acute myeloid leukemia (CN-AML) is still a challenging entity. The discovery of IDH1 mutation in AML together with the frequent co-mutations; NPM1 and FLT3-ITD throughs a new insight into the pathogenesis and outcome of CN-AML. Recently, there has been an increasing number of recurring mutations in other genes for which the forecasting effect is still required. Despite the large number of risk variables established, there are relatively few prognostic indicators that can help in treatment decisions in AML patients. This study aimed at recording the frequency of IDH1 and NPM1 mutations in newly diagnosed AML and, dual clinicopathological significance. IDH1 and NPM1 mutations were analyzed using High-Resolution Melting curve analysis PCR in 78 newly diagnosed AML patients; 30 pediatric and 48 adult AML patients. IDH1 mutation was detected in 6 out of the 48 adult AML cases (12.5%) and all of them had intermediate cytogenetic prognostic stratification. 5/6 mutant IDH1 patients showed NPM1 co-mutation (P-value= 0.008). Mutant IDH1 patients showed significant resistance to induction therapy (P-value <0.001) and even those who achieved complete remission were relapsed later. Within the intermediate cytogenetic group, the IDH1 mutated patients had short overall survival (HR 12.9, 95% CI (3.1- 53.45) and event-free survival (HR 15.7, 95% CI (2.99-82.72) and P-value <0.001). IDH1 mutation is closely linked to the intermediate cytogenetic stratified group and in particular old age patients and has a great impact on their survival.


2021 ◽  
Vol 8 (1) ◽  
Author(s):  
Yukito Maeda ◽  
Yuka Yamamoto ◽  
Takashi Norikane ◽  
Katsuya Mitamura ◽  
Tetsuhiro Hatakeyama ◽  
...  

Abstract Background The present study tested the possible utility of fractal analysis from l-[methyl-11C]-methionine (MET) uptake in patients with newly diagnosed gliomas for differentiating glioma, especially in relation to isocitrate dehydrogenase 1 (IDH1) mutation status, and as compared with the conventional standardized uptake value (SUV) parameters. Methods Investigations of MET PET/CT were performed retrospectively in 47 patients with newly diagnosed glioma. Tumors were divided into three groups: lower grade glioma (IDH1-mutant diffuse astrocytoma and IDH1-mutant anaplastic astrocytoma), higher grade glioma (IDH1-wildtype diffuse astrocytoma and IDH1-wildtype anaplastic astrocytoma), and glioblastoma. The fractal dimension for tumor, maximum SUV (SUVmax) for tumor (T) and mean SUV for normal contralateral hemisphere (N) were calculated, and the tumor-to-normal (T/N) ratio was determined. Metabolic tumor volume (MTV) and total lesion MET uptake (TLMU) were also measured. Results There were significant differences in SUVmax (p = 0.006) and T/N ratio (p = 0.02) between lower grade glioma and glioblastoma. There were no significant differences among any of the three groups in MTV or TLMU. Significant differences were obtained in the fractal dimension between lower grade glioma and higher grade glioma (p = 0.006) and glioblastoma (p < 0.001). Conclusions The results of this preliminary study in a small patient population suggest that the fractal dimension using MET PET in patients with newly diagnosed gliomas is useful for differentiating glioma, especially in relation to IDH1 mutation status, which has not been possible with SUV parameters.


Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 2878-2878
Author(s):  
Wen Yao ◽  
Liangquan Geng ◽  
Dongyao Wang ◽  
Huilan Liu ◽  
Baolin Tang ◽  
...  

Abstract Objective: We observed the efficacy and safety of umbilical cord blood microtransplantation (UCBMT) in the treatment of newly diagnosed with acute myeloid leukemia (AML) in the elderly. Methods: Prospective one-arm phase I clinical study. The patients should meet the following criteria: 60-80-year-old; newly diagnosed AML; receive the treatment of chemotherapy combined with UCBMT. Result: In total, 11 patients newly diagnosed with AML received chemotherapy in combination with UCBMT, from November, 2019 to January, 2021, including 7 males and 4 females. The average age was 71 (60-80). For the patients, 7 cases with normal chromosome karyotype, and 2 cases with +8 chromosome, 1 case with 7q- chromosome, and 1 case with karyotype of monomer. In the 7 patients with normal chromosome karyotype, 3 cases were FMS-liketyrosine kinease 3 (FLT3) positive (2 of them in combination with nucleophosmin 1 (NPM1) mutation); in addition, in 4 patients of the 7, one showed double mutation of CEBPA, one showed NPM1 mutation, one showed IDH1 mutation, and one showed IDH2 mutation. In 4 patients with chromosomal abnormalities, one patient showed no special gene, one patient showed ASXL1 mutation, one patient was IDH1 mutation, and one patient was TP53 mutation. All of the patients were treated with IA (IDA 8-10 mg/ m 2/day x 3 days, cytarabine 100 mg/ m 2/day x 7 days) for inducing chemotherapy. For the patients with 60-70-year-old, they were treated with IDA (8 mg/ m 2/day); and for the patients with 70-80-year-old, they were treated with darubicin (10 mg/ m 2/day). In the consolidation phase, the patients were treated with cytarabine (1 g/ m 2, q12h) for 3 consecutive days. There were 3 courses of consolidation chemotherapy. Next, patients received single unrelated cord blood transplantation (UCBT) from China's public umbilical cord blood bank, HLA matching was performed for all patients before treatment. A total of 4 units of UCB with HLA 0-3/6(HLA-A,-B,-DR)matching and the ABO blood type matched with the patient were transfused after induction and consolidation chemotherapy for 24-48 hours, then with follow-up. At the same time, the immunological characteristics of these patients were fully analyzed. We demonstrated that, 8 of 11 patients received one course of induction chemotherapy, and achieved a complete response. The complete response rate was 72.7%. What's more, the median time for neutrophils ≥ 0.5 x 10 9/L and platelete ≥ 20 x 10 9/L was 12 days. There were no treatment-related deaths during induction therapy. The median follow-up was 14 (7-31) months. 1 patient showed monomer karyotype with P53 gene mutation, and got complete remission after one course of induction chemotherapy with IA. However, the patient died for AML recurred. For the other 10 patients, they were alive, and the OS of 1 year was 89.8%. Moreover, we found the expression of PD-1 on CD8 +T cells decreased, while the expression of CD38 increased after therapy. Besides, the proportion of NKp30 +NK cells, as well as the IFN-γ +TFN-α +NK cells increased significantly. Conclusion: UCBMT therapy for newly diagnosed elderly AML patients could accelerate the recovery of hematopoietic function and improve the safety of chemotherapy. This method is effective and worthy of further promotion. Disclosures No relevant conflicts of interest to declare.


Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 4469-4469
Author(s):  
Amy Song ◽  
Jasmine Mahajan ◽  
Nivetha Srinivasan ◽  
Kendra Sweet ◽  
David A. Sallman ◽  
...  

Abstract Introduction: Isocitrate dehydrogenase 1 (IDH1) gene is mutated in 7-14% of acute myeloid leukemia (AML) patients. IDH1 encodes for an enzyme that catalyzes the conversion of isocitrate to α- ketoglutarate. IDH1 mutation leads to accumulation of the oncometabolite 2-hydroxyglutarate. Clonal evolutionary dynamics of IDH1 mutations in AML have not been clearly characterized. The introduction of targeted small-molecule therapy, Ivosidenib, in AML treatment underscores the significance of understanding the topography of clonal dynamics in IDH1-mutated AML to optimize precision medicine. Methods: We analyzed ~6000 patients with next-generation sequencing (NGS) data and identified 107 patients with IDH1 mutated AML. Disease status was determined for each NGS test date by manual chart review. IDH1 mutation status was characterized during course of AML at diagnosis, remission, relapse, and with persistent disease. Cytogenic risk category was determined using ELN 2017 guidelines. Kaplan Meier survival analysis and log-rank test were used to determine significant differences in overall survival among patient groups. Results: Of the 107 total patients, 39 patients (36%) had AML with myelodysplastic-related changes (AML-MRC) and 39 patients (36%) had AML-NOS. The most frequently co-mutated genes were SRSF2, DNMT3A, ASXL1, RUNX1, NRAS, BCOR, STAG2, NPM1, JAK2, and FLT-3 in order of frequency. Of the total patients, 74 patients (69%) had good cytogenetics, 17 patients (16%) had intermediate cytogenetics, and 16 patients (15%) had poor/very poor cytogenetics. Among the patients with IDH1-mutated AML, 85 patients (79%) were IDH1-positive at initial diagnosis, while 22 patients (21%) were IDH1- negative at diagnosis and acquired the mutation later in disease course. Of those 22 patients, 18 patients gained the mutation in the setting of persistent disease, 3 patients at remission, and 1 patient at relapse. In those with persistent AML (n=42), 30 patients (71%) remained IDH1-positive while 12 patients (29%) lost the mutation. In those achieving remission (n=66), 12 patients (18%) who were IDH1-positive remained IDH1-positive while 51 patients (77%) cleared the mutation. In those with relapsed disease (n= 21), 17 patients (81%) with IDH1-positive AML remained IDH1-positive while 4 patients (19%) lost the mutation at relapse. There were no significant differences in median overall survival in patients who were positive or negative for IDH1 mutations at diagnosis, positive or negative with disease persistence, or among patients who remained IDH1-positive or lost the IDH1 mutation at disease relapse. Patients that were IDH1-positive at diagnosis were more likely to have poorer cytogenetics than patients who were IDH1-negative at diagnosis (p=0.0016). Conclusion: In summary, this study found that IDH1 mutations are unstable throughout the course of AML and periodic genetic testing of AML patients is necessary for optimizing precision medicine approaches. In disease remission, most patients (77%) cleared the IDH1 mutation. In the relapse setting, 81% of patients retained IDH1-positive status. Our study, the largest of its kind to our knowledge, shows that serial genomic profiling for the IDH1 mutation across disease course may be beneficial in helping to tailor targeted therapy for IDH1+ AML. Disclosures Sweet: Bristol Meyers Squibb: Honoraria, Membership on an entity's Board of Directors or advisory committees; AROG: Membership on an entity's Board of Directors or advisory committees; Gilead: Membership on an entity's Board of Directors or advisory committees; Astellas: Consultancy, Membership on an entity's Board of Directors or advisory committees; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees. Sallman: Kite: Membership on an entity's Board of Directors or advisory committees; Agios: Membership on an entity's Board of Directors or advisory committees; Aprea: Membership on an entity's Board of Directors or advisory committees, Research Funding; Bristol-Myers Squibb: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Intellia: Membership on an entity's Board of Directors or advisory committees; Magenta: Consultancy; Incyte: Speakers Bureau; AbbVie: Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees; Takeda: Consultancy; Shattuck Labs: Membership on an entity's Board of Directors or advisory committees; Syndax: Membership on an entity's Board of Directors or advisory committees. Hussaini: Adaptive: Consultancy, Honoraria, Speakers Bureau; Stemline: Consultancy; Amgen: Consultancy; Seattle Genetics: Consultancy; Celegene: Consultancy; Decibio: Consultancy; Guidepoint: Consultancy; Bluprint Medicine: Consultancy.


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